Microfluidic devices have been designed that are useful in performing high throughput assays useful for biological and chemical screening experiments. Both glass and polymer microfluidic devices comprising microfluidic channels and microfluidic wells are now available. For example, polymer microfluidic devices are provided in PCT application WO 98/46438, “Controlled Fluid Transport in Microfabricated Polymeric Substrates,” by Parce et al., and glass devices are set forth in a number of publications and patents set forth herein.
Continuous flow microfluidic systems are set forth in, e.g., published PCT application WO 98/00231, by Parce et al. These devices are useful, for example, in screening large numbers of different compounds for their effects on a variety of chemical and biochemical systems. The devices include a series of channels fabricated on or within the devices. The devices also can include reservoirs, fluidly connected to the channels, that can be used to introduce a number of test compounds into the sample channels and thus perform the assays. Interfacing mechanisms, such as electropipettors, can be incorporated into these high-throughput systems for transporting samples into wells or microfluidic channels. See, e.g., “Electropipettor and Compensation Means for Electrophoretic Bias,” U.S. Pat. No. 5,799,868, by Parce et al.
Microfluidic systems for fast, accurate and low cost electrophoretic analysis of materials in the fields of chemistry, biochemistry, biotechnology, molecular biology and numerous other fields, are described in U.S. Pat. No. 5,699,157 by Parce et al. Techniques for transporting materials through microfluidic channels using electrokinetic forces were described in “Electropipettor and Compensation Means for Electrophoretic Bias,” U.S. Pat. No. 5,799,868, by Parce et al.
Movement of material through microfluidic channels was further described in “Variable Control of Electroosmotic and/or Electrophoretic Forces within a Fluid Containing Structure Via Electrical Forces,” U.S. Pat. No. 5,800,690, by Chow et al. In this patent, various power supplies, such as a time-multiplexed power supplies that vary the voltage on the system, are described that are used to provide control over the fluid movement in a microfluidic device.
Electroosmotic pressure flow has also been described to provide other ways to modulate microfluidic flow rates. For example, these methods can involve providing an effective zwitterionic compound in the fluid containing the material to be transported. See, e.g., Published PCT application, WO 98/45929 by Nikiforov at el. Additionally, Published PCT application, WO 98/56956 by Kopf-Sill et al. provides methods of correcting for variable velocity in microfluidic devices.
Channel dimensions have also been varied to provide further control over the movement of fluid through the channels, such as in “Microfluidic Systems Incorporating Varied Channel Dimensions,” See, e.g., U.S. Pat. No. 5,842,787, by Kopf-Sill et al.
Although corrections can be made for variable velocities, see, e.g., Published PCT application, WO 98/56956, by Kopf-Sill et al., it is advantageous to be able to rapidly and easily modulate the velocity or flow rate of a component in a microfluidic device. There exists a need for high throughput screening methods, and associated equipment and devices, that are capable of performing repeated, accurate assay, operating at very small volumes and at regulated and/or continuous flow rates. These assays are particularly useful for high throughput screening, as well as for a variety of research applications.
The present invention meets these and a variety of other needs. In particular, the present invention provides novel methods and apparatuses for performing assays with continuous or discontinuous flow rates, as well as other apparatus methods and integrated systems, which will be apparent upon complete review of the disclosure.